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Lung cancer stands as one of the most lethal diseases and is the foremost cause of cancer-related mortalities worldwide. The pathophysiology of lung cancer is multifaceted, and it includes multiple cell signaling pathways and other complex factors such as oxidative stress and genetics. The association of HPV with lung carcinogenesis was first proposed in 1979, and since then, scientists worldwide have been putting forward several hypotheses to establish a relationship between this virus and lung cancer. Although studies have reported the presence of HPV in lung cancer, the exact mechanism of entry and the route of transmission have not been elucidated clearly till date. Numerous studies across the globe have detected differentially expressed HPV oncoproteins in lung cancer patients and found their association with the critical cell signaling pathways that leads to the development and progression of lung cancer. Many reports have also provided evidence stating the involvement of HPV in determining the survival status of lung cancer patients. The present review recapitulates the studies evincing the association of HPV and lung cancer, its route of transmission and mechanism of action; the detection of the virus and treatment opportunities for HPV-positive lung cancer; and the severity associated with this disease. Therefore, this will provide an explicit idea and would help to develop preventive measures and specific as well as effective treatment for HPV-associated lung carcinogenesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Aortic stenosis (AS) is characterized by calcification and fibrosis. The ability to quantify these processes simultaneously has been limited with previous imaging methods., Objectives: The purpose of this study was to evaluate the aortic valve fibrocalcific volume by computed tomography (CT) angiography in patients with AS, in particular, to assess its reproducibility, association with histology and disease severity, and ability to predict/track progression., Methods: In 136 patients with AS, fibrocalcific volume was calculated on CT angiograms at baseline and after 1 year. CT attenuation distributions were analyzed using Gaussian-mixture-modeling to derive thresholds for tissue types enabling the quantification of calcific, noncalcific, and fibrocalcific volumes. Scan-rescan reproducibility was assessed and validation provided against histology and in an external cohort., Results: Fibrocalcific volume measurements took 5.8 ± 1.0 min/scan, demonstrating good correlation with ex vivo valve weight (r = 0.51; P < 0.001) and excellent scan-rescan reproducibility (mean difference -1%, limits of agreement -4.5% to 2.8%). Baseline fibrocalcific volumes correlated with mean gradient on echocardiography in both male and female participants (rho = 0.64 and 0.69, respectively; both P < 0.001) and in the external validation cohort (n = 66, rho = 0.58; P < 0.001). The relationship was driven principally by calcific volume in men and fibrotic volume in women. After 1 year, fibrocalcific volume increased by 17% and correlated with progression in mean gradient (rho = 0.32; P = 0.003). Baseline fibrocalcific volume was the strongest predictor of subsequent mean gradient progression, with a particularly strong association in female patients (rho = 0.75; P < 0.001)., Conclusions: The aortic valve fibrocalcific volume provides an anatomic assessment of AS severity that can track disease progression precisely. It correlates with disease severity and hemodynamic progression in both male and female patients., Competing Interests: Funding Support and Author Disclosures The SALTIRE 2 trial was funded by the British Heart Foundation (FS/14/78/31020). This work was partially supported by a grant from the Korea Health Technology R and D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant number HI22C0154 to Dr Lee). Dr Joshi has received funding from the British Heart Foundation through a Clinical Research Training Fellowship and Research Excellence Award (FS/CRTF/20/24087 and RE/18/5/34216). Dr Williams is supported by the British Heart Foundation (FS/ICRF/20/26002); and has given talks for Canon Medical Systems, Siemens Healthineers and Novartis. Dr Newby is supported by the British Heart Foundation (CH/09/002, RG/20/10/34966, RE/18/5/34216, CH/F/21/90010); and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr Dweck is supported by the British Heart Foundation (FS/SCRF/21/32010); is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA); has received speaker fees from Pfizer, Radcliffe Cardiology, Bristol Myers Squibb, Edwards, and Novartis; has received consultancy fees from Novartis, Jupiter Bioventures, Beren, and Silence therapeutics; and is Director of the Imaging Corelab at the University of Edinburgh. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Angiographic assessment of left main coronary artery (LMCA) stenosis severity can be unreliable. In cases of ambiguity, intravascular ultrasound (IVUS) can be utilised with a minimal lumen area (MLA) of ≥6 ​mm 2 an accepted threshold for safe deferral of revascularization. We sought to assess whether quantitative computer tomography coronary angiography (CTCA) measures could assist clinicians making LMCA revascularization decisions when compared with IVUS as gold standard., Methods: Consecutive patients undergoing IVUS assessment of angiographically intermediate LMCA stenosis were included. All patients had undergone 320-slice CTCA <90 days prior to IVUS imaging. Offline quantitative assessment of IVUS- and CT-derived measures were undertaken with the cohort divided into those with significant (s-LMCA) versus non-significant (ns-LMCA) disease using the accepted IVUS threshold., Results: Fifty-eight patients were included, with no difference in mean age (61.5 ​± ​12.2 vs. 59.7 ​± ​11.9 years, p ​= ​0.57), diabetic status (24.2% vs 16.0%, p ​= ​0.44) or other baseline demographics between groups. Patients with ns-LMCA had larger CT luminal area (8.64 ​± ​3.91 vs. 5.41 ​± ​1.54 ​mm 2 , p ​< ​0.001), larger minimal lumen diameter (MLD) (3.25 ​± ​0.74 vs. 2.56 ​± ​0.38 ​mm, p ​< ​0.001) and lower area stenosis (45.74 ​± ​18.10 vs. 60.93 ​± ​14.68%, p ​= ​0.001). There was a significant positive correlation between CTCA and IVUS MLA (r ​= ​0.68, p ​< ​0.001) and MLD (r ​= ​0.67, p ​< ​0.001). ROC analysis demonstrated CTCA MLA cut-off <8.29 ​mm 2 provides the greatest negative predictive value and sensitivity in predicting the presence of significant LMCA disease., Conclusion: CTCA derived MLA and MLD have a strong correlation with IVUS. A CTCA derived MLA cut-off <8.29 ​mm 2 showed greatest clinical utility for predicting the need for further assessment, based on IVUS gold standard., Competing Interests: Declaration of competing interest The authors have no specific conflict of interests to declare with respect to this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Recent studies suggest that the application of exercise activity questionnaires, including the use of a single-item exercise question, can be additive to the prognostic efficacy of imaging findings. This study aims to evaluate the prognostic efficacy of exercise activity in patients undergoing coronary computed tomography angiography (CCTA)., Methods and Results: We assessed 9772 patients who underwent CCTA at a single center between 2007 and 2020. Patients were divided into 4 groups of physical activity as no exercise (n ​= ​1643, 17%), mild exercise (n ​= ​3156, 32%), moderate exercise (n ​= ​3542, 36%), and high exercise (n ​= ​1431,15%), based on a single-item self-reported questionnaire. Coronary stenosis was categorized as no (0%), non-obstructive (1-49%), borderline (50-69%), and obstructive (≥70%). During a median follow-up of 4.64 (IQR 1.53-7.89) years, 490 (7.6%) died. There was a stepwise inverse relationship between exercise activity and mortality (p ​< ​0.001). Compared with the high activity group, the no activity group had a 3-fold higher mortality risk (HR: 3.3, 95%CI (1.94-5.63), p ​< ​0.001) after adjustment for age, clinical risk factors, symptoms, and statin use. For any level of CCTA stenosis, mortality rates were inversely associated with the degree of patients' exercise activity. The risk of all-cause mortality was similar among the patients with obstructive stenosis with high exercise versus those with no coronary stenosis but no exercise activity (p ​= ​0.912)., Conclusion: Physical activity as assessed by a single-item self-reported questionnaire is a strong stepwise inverse predictor of mortality risk among patients undergoing CCTA., Competing Interests: Declaration of competing interest All authors declare no conflict of interests, (Copyright © 2024. Published by Elsevier Inc.)

Background: Computed tomography attenuation correction (CTAC) improves perfusion quantification of hybrid myocardial perfusion imaging by correcting for attenuation artifacts. Artificial intelligence (AI) can automatically measure coronary artery calcium (CAC) from CTAC to improve risk prediction but could potentially derive additional anatomic features., Objectives: The authors evaluated AI-based derivation of cardiac anatomy from CTAC and assessed its added prognostic utility., Methods: The authors considered consecutive patients without known coronary artery disease who underwent single-photon emission computed tomography/computed tomography (CT) myocardial perfusion imaging at 3 separate centers. Previously validated AI models were used to segment CAC and cardiac structures (left atrium, left ventricle, right atrium, right ventricular volume, and left ventricular [LV] mass) from CTAC. They evaluated associations with major adverse cardiovascular events (MACEs), which included death, myocardial infarction, unstable angina, or revascularization., Results: In total, 7,613 patients were included with a median age of 64 years. During a median follow-up of 2.4 years (IQR: 1.3-3.4 years), MACEs occurred in 1,045 (13.7%) patients. Fully automated AI processing took an average of 6.2 ± 0.2 seconds for CAC and 15.8 ± 3.2 seconds for cardiac volumes and LV mass. Patients in the highest quartile of LV mass and left atrium, LV, right atrium, and right ventricular volume were at significantly increased risk of MACEs compared to patients in the lowest quartile, with HR ranging from 1.46 to 3.31. The addition of all CT-based volumes and CT-based LV mass improved the continuous net reclassification index by 23.1%., Conclusions: AI can automatically derive LV mass and cardiac chamber volumes from CT attenuation imaging, significantly improving cardiovascular risk assessment for hybrid perfusion imaging., Competing Interests: Funding Support and Author Disclosures This research was supported in part by the National Heart, Lung, and Blood Institute at the National Institutes of Health grant R35HL161195 (Principal Investigator: Dr Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mr Kavanagh has received software royalties for QPS software at Cedars-Sinai Medical Center. Dr Miller has received consulting fees and research support from Pfizer; and has served as a consultant for GE Healthcare. Dr Newby is supported by the British Heart Foundation; is a recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA); and has received honoraria for consultancy and lectures from AstraZeneca. Dr Berman has received software royalties for QPS software at Cedars-Sinai Medical Center; and has served as a consultant for GE Healthcare. Dr Slomka has received software royalties for QPS software at Cedars-Sina Medical Center, research grant support from Siemens Medical Systems, and consulting fees from Synektik., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Positive remodeling is an integral part of the vascular adaptation process during the development of atherosclerosis, which can be detected by coronary computed tomography angiography (CTA)., Methods: A total of 426 patients who underwent both coronary CTA and optical coherence tomography (OCT) were included. Four machine learning (ML) models, gradient boosting machine (GBM), random forest (RF), deep learning (DL), and support vector machine (SVM), were employed to detect specific plaque features. A total of 15 plaque features assessed by OCT were analyzed. The variable importance ranking was used to identify the features most closely associated with positive remodeling., Results: In the variable importance ranking, lipid index and maximal calcification arc were consistently ranked high across all four ML models. Lipid index and maximal calcification arc were correlated with positive remodeling, showing pronounced influence at the lower range and diminishing influence at the higher range. Patients with more plaques with positive remodeling throughout their entire coronary trees had higher low-density lipoprotein cholesterol levels and were associated with a higher incidence of cardiovascular events during 5-year follow-up (Hazard ratio 2.10 [1.26-3.48], P ​= ​0.004)., Conclusion: Greater lipid accumulation and less calcium burden were important features associated with positive remodeling in the coronary arteries. The number of coronary plaques with positive remodeling was associated with a higher incidence of cardiovascular events., Competing Interests: Declaration of competing interest Dr. Jang reports receiving educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems, Inc. Dr. Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

The present work represents a Fluorescence Resonance Energy Transfer (FRET) based sensing method for detecting Gunshot Residue (GSR) components. Two laser dyes Acf and RhB have been used as donor and acceptor respectively in the FRET pair. The real sample was collected after test firing in a forensic science laboratory. On the other hand, a standard GSR solution has been prepared in the laboratory. For the preparation of standard GSR solutions, we used the water solutions of the salts BaCl 2 , SbCl 3, and Pb(NO 3 ) 2 . The FRET efficiency was measured between Acf and RhB to sense the presence of GSR components (Pb +2 , Ba +2 , and Sb +3 ) in both real sample and standard solution by mixing the salts in aqueous solution. It has been observed that the FRET efficiency systematically decreases in the presence of GSR components. To amplify the FRET efficiency of the dye pair, inorganic clay dispersion (laponite) was used. The enhancement in FRET efficiency represents a better sensitivity of the proposed sensor. The current sensor is useful for the quantification of concentrations of the GSR components in a real sample., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cardiac computed tomography quantification of extracellular volume fraction (CT-ECV) is an emerging biomarker of myocardial fibrosis which has demonstrated high reproducibility, diagnostic and prognostic utility. However, there has been wide variation in the CT-ECV protocol in the literature and useful disease cut-offs are yet to be established. The objectives of this meta-analysis were to describe mean CT-ECV estimates and to estimate the effect of CT-ECV protocol parameters on between-study variation., Methods: We conducted a meta-analysis of studies assessing CT-ECV in healthy and diseased participants. We used meta-analytic methods to pool estimates of CT-ECV and performed meta-regression to identify the contribution of protocol parameters to CT-ECV heterogeneity., Results: Thirteen studies had a total of 248 healthy participants who underwent CT-ECV assessment. Studies of healthy participants had high variation in CT-ECV protocol parameters. The pooled estimate of CT-ECV in healthy participants was 27.6% (95%CI 25.7%-29.4%) with significant heterogeneity (I 2  ​= ​93%) compared to 50.2% (95%CI 46.2%-54.2%) in amyloidosis, 31.2% (28.5%-33.8%) in severe aortic stenosis and 36.9% (31.6%-42.3%) in non-ischaemic dilated cardiomyopathies. Meta-regression revealed that CT protocol parameters account for approximately 25% of the heterogeneity in CT-ECV estimates., Conclusion: CT-ECV estimates for healthy individuals vary widely in the literature and there is significant overlap with estimates in cardiac disease. One quarter of this heterogeneity is explained by differences in CT-ECV protocol parameters. Standardization of CT-ECV protocols is necessary for widespread implementation of CT-ECV assessment for diagnosis and prognosis., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024. Published by Elsevier Inc.)

In current clinical practice, qualitative or semi-quantitative measures are primarily used to report coronary artery disease on cardiac CT. With advancements in cardiac CT technology and automated post-processing tools, quantitative measures of coronary disease severity have become more broadly available. Quantitative coronary CT angiography has great potential value for clinical management of patients, but also for research. This document aims to provide definitions and standards for the performance and reporting of quantitative measures of coronary artery disease by cardiac CT., Competing Interests: Declaration of competing interest Héctor M. García-García reports the following Institutional grant support: Biotronik, Boston Scientific, Medtronic, Abbott, Neovasc, Shockwave, Phillips and Corflow; Consultancy fee from Boston Scientific, Abbott and Amgen. Koen Nieman acknowledges support from the NIH (NIH R01- HL141712; NIH R01 - HL146754), and reports unrestricted institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc, Novartis unrelated to this work, consulting for Novartis and Siemens Medical Solutions USA, Artrya, Cleerly, Elucid, and equity in Lumen Therapeutics. Maksymilian P. Opolski reports institutional grant support from B. Braun; consulting for Boston Scientific and proctorship for Boston Scientific, Terumo and Biotronik. Michelle Williams has given talks for Canon Medical Systems, Siemens Healthineers and Novartis. Damini Dey has received software royalties from Cedars-Sinai Medical Center and is supported by grants from the NIH/NHLBI (1R01HL148787-01A1 and 1R01HL151266). Jonathon Leipsic is a consultant and holds stock options in HeartFlow Inc., is a consultant to Circle CVI and has received modest corelab personal fees from Arineta and has received modest speaking fees from GE Healthcare and Philips HealthCare. Michael T Lu reports institutional research support from the American Heart Association (18UNPG34030172; 810,966), AstraZeneca, Ionis, Johnson & Johnson Innovation, Kowa, the National Academy of Medicine, and the NIH (U01HL123339; U24HL164284; R33HL141047; R01HL164629). Maros Ferencik received grant support from the American Heart Association and National Institutes of Health. Maros Ferencik received consulting fees HeartFlow, Elucid, Siemens Healthineers., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: High-intensity plaque (HIP) on magnetic resonance imaging (MRI) has been documented as a powerful predictor of periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI). Despite the recent proposal of three-dimensional HIP quantification to enhance the predictive capability, the conventional pulse sequence, which necessitates the separate acquisition of anatomical reference images, hinders accurate three-dimensional segmentation along the coronary vasculature. Coronary atherosclerosis T 1 -weighted characterization (CATCH) enables the simultaneous acquisition of inherently coregistered dark-blood plaque and bright-blood coronary artery images. We aimed to develop a novel HIP quantification approach using CATCH and to ascertain its superior predictive performance compared to the conventional two-dimensional assessment based on plaque-to-myocardium signal intensity ratio (PMR)., Methods: In this prospective study, CATCH MRI was conducted before elective stent implantation in 137 lesions from 125 patients. On CATCH images, dedicated software automatically generated tubular three-dimensional volumes of interest on the dark-blood plaque images along the coronary vasculature, based on the precisely matched bright-blood coronary artery images, and subsequently computed PMR and HIP volume (HIP vol ). Specifically, HIP vol was calculated as the volume of voxels with signal intensity exceeding that of the myocardium, weighted by their respective signal intensities. PMI was defined as post-PCI cardiac troponin-T > 5 × the upper reference limit., Results: The entire analysis process was completed within 3 min per lesion. PMI occurred in 44 lesions. Based on the receiver operating characteristic curve analysis, HIP vol outperformed PMR for predicting PMI (C-statistics, 0.870 [95% CI, 0.805-0.936] vs. 0.787 [95% CI, 0.706-0.868]; p = 0.001). This result was primarily driven by the higher sensitivity HIP vol offered: 0.886 (95% CI, 0.754-0.962) vs. 0.750 for PMR (95% CI, 0.597-0.868; p = 0.034). Multivariable analysis identified HIP vol as an independent predictor of PMI (odds ratio, 1.15 per 10-μL increase; 95% CI, 1.01-1.30, p = 0.035)., Conclusions: Our semi-automated method of analyzing coronary plaque using CATCH MRI provided rapid HIP quantification. Three-dimensional assessment using this approach had a better ability to predict PMI than conventional two-dimensional assessment., Competing Interests: Declaration of Competing Interest Yoshiaki Komori is an employee of Siemens Japan KK. Other authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Psoriasis is a prevalent inflammatory skin condition characterized by erythematous plaques with scaling. Recent research has demonstrated an increased risk of cardiovascular diseases in patients with psoriasis; however, current evidence on atrial fibrillation (AF) risk in psoriasis is limited., Materials and Methods: A systematic literature search was performed on major bibliographic databases to retrieve studies that evaluated AF risk in patients with psoriasis. The DerSimonian and Laird random effects model was used to pool the hazard ratios (HR) with 95 % confidence intervals (CI). Subgroup analysis was conducted by dividing the patients into mild and severe psoriasis groups. Publication bias was assessed by visual inspection and Egger's regression test. Statistical significance was set at p < 0.05., Results: Seven studies were included, with 10,974,668 participants (1,94,230 in the psoriasis group and 10,780,439 in the control group). Patients with psoriasis had a significantly higher risk of AF [Pooled HR: 1.28; 95 % CI: 1.20, 1.36; p < 0.00001]. In subgroup analysis, patients with severe psoriasis [HR: 1.32; 95 % CI: 1.23, 1.42; p < 0.00001] demonstrated a slightly higher risk of AF, although statistically insignificant (p = 0.17), than the mild psoriasis group [HR: 1.21; 95 % CI: 1.10, 1.33; p < 0.0001]. Egger's regression test showed no statistically significant publication bias (p = 0.24)., Conclusion: Our analysis demonstrated that patients with psoriasis are at a significantly higher risk of AF and hence should be closely monitored for AF. Further large-scale and multicenter randomized trials are warranted to validate the robustness of our findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Coronary artery calcium (CAC), thoracic aorta calcification (TAC), non-alcoholic fatty liver disease (NAFLD), and epicardial adipose tissue (EAT) are associated with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF)., Objectives: We aimed to determine whether these cardiometabolic and atherosclerotic risk factors identified by non-contrast chest computed tomography (CT) are associated with HF hospitalizations in patients with LDL-C≥ 190 mg/dL., Methods: We conducted a retrospective cohort analysis of patients with LDL-C ≥190 mg/dL, aged ≥40 years without established ASCVD or HF, who had a non-contrast chest CT within 3 years of LDL-C measurement. Ordinal CAC, ordinal TAC, EAT, and NAFLD were measured. Kaplan-Meier curves and multivariable Cox regression models were built to ascertain the association with HF hospitalization., Results: We included 762 patients with median age 60 (53-68) years, 68% (n=520) female, and median LDL-C level of 203 (194-216) mg/dL. Patients were followed for 4.7 (interquartile range 2.75-6.16) years, and 107 (14%) had a HF hospitalization. Overall, 355 (47%) patients had CAC=0, 210 (28%) had TAC=0, 116 (15%) had NAFLD, and median EAT was 79 mL (49-114). Moderate-Severe CAC (log-rank p<0.001) and TAC (log-rank p=0.006) groups were associated with increased HF hospitalizations. This association persisted when considering myocardial infarction (MI) as a competing risk. NAFLD and EAT volume were not associated with HF., Conclusions: In patients without established ASCVD and LDL-C≥190 mg/dL, CAC was independently associated with increased HF hospitalizations while TAC, NAFLD, and EAT were not., (Copyright © 2024. Published by Elsevier Inc.)

Background: Despite its potential benefits, the utilization of stress-only protocol in clinical practice has been limited. We report utilizing stress-first single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)., Methods: We assessed 12,472 patients who were referred for SPECT-MPI between 2013 and 2020. The temporal changes in frequency of stress-only imaging were assessed according to risk factors, mode of stress, prior coronary artery disease (CAD) history, left ventricular function, and symptom status. The clinical endpoint was all-cause mortality., Results: In our lab, stress/rest SPECT-MPI in place of rest/stress SPECT-MPI was first introduced in November 2011 and was performed more commonly than rest/stress imaging after 2013. Stress-only SPECT-MPI scanning has been performed in 30-34% of our SPECT-MPI studies since 2013 (i.e.. 31.7% in 2013 and 33.6% in 2020). During the study period, we routinely used two-position imaging (additional prone or upright imaging) to reduce attenuation and motion artifact and introduced SPECT/CT scanner in 2018. The rate of stress-only study remained consistent before and after implementing the SPECT/CT scanner. The frequency of stress-only imaging was 43% among patients without a history of prior CAD and 19% among those with a prior CAD history. Among patients undergoing treadmill exercise, the frequency of stress-only imaging was 48%, while 32% among patients undergoing pharmacologic stress test. In multivariate Cox analysis, there was no significant difference in mortality risk between stress-only and stress/rest protocols in patients with normal SPECT-MPI results (p = 0.271)., Conclusion: Implementation of a stress-first imaging protocol has consistently resulted in safe cancellation of 30% of rest SPECT-MPI studies., Competing Interests: Declaration of competing interest Dr. Berman participates in software royalties for QPS software at Cedars-Sinai Medical Center. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ample evidence suggests that female smokers face a greater risk of smoking-related health problems than male smokers. Due to the growing number of young smokers in the United States, there has been limited information on the effects of smoking on young female smokers over the past decade., Methods: Hospitalizations of young (18-44 years) female tobacco smokers were identified using the National Inpatient Sample datasets from 2007 and 2017. We compared differences in admission frequency, comorbidity burden, in-hospital outcomes [all-cause mortality and major adverse cardiac events (MACE)], and resource utilization between two young cohorts separated by 10 years., Results: In 2007, there were 665,901 admissions among young female smokers (median age: 35), compared to 1,224,479 admissions (median age: 32) in 2017. In both cohorts, white female smokers accounted for most admissions, followed by blacks. In 2017, the prevalence of alcohol abuse, hyperlipidemia, uncomplicated diabetes, and chronic pulmonary disease decreased relative to the 2007 cohort, whereas the prevalence of deficiency and chronic blood loss anemias, diabetes with complications, drug abuse, hypertension, congestive heart failure, depression, liver disease, and obesity increased significantly (p<0.001). The 2017 cohort had significantly higher odds of all-cause mortality [aOR 1.25 (95%CI: 1.16-1.35)] and a higher risk of MACE [aOR 1.17 (95%CI:1.14-1.20)] upon multivariable adjustment. (p<0.001). Comparatively, the 2017 cohort had fewer routine discharges and higher home healthcare needs than the 2007 cohort., Conclusions: In this decade-apart analysis, the study reveals rising trends in the burden of comorbidities, MACE, and healthcare resource utilization in admissions (regardless of the primary cause) among relatively younger female smokers. It is crucial to educate young female smokers about the detrimental effects of tobacco and polysubstance abuse on cardiovascular outcomes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Improper disposal practices have caused environmental disruptions, possessing by heavy metal ions and radioactive elements in water and soil, where the innovative and sustainable remediation strategies are significantly imperative in last few decades. Microbially induced carbonate precipitation (MICP) has emerged as a pioneering technology for remediating contaminated soil and water. Generally, MICP employs urease-producing microorganisms to decompose urea (NH 2 CONH 2 ) into ammonium (NH 4 + and carbon dioxide (CO 2 ), thereby increasing pH levels and inducing carbonate precipitation (CO 3 2- ), and effectively removing remove contaminants. Nonetheless, the intricate mechanism underlying heavy metal mineralization poses a significant challenge, constraining its application in contaminants engineering, particularly in the context of prolonged heavy metal leaching over time and its efficacy in adverse environmental conditions. This review provides a comprehensive idea of recent development of MICP and its application in environmental engineering, examining metabolic pathways, mineral precipitation mechanisms, and environmental factors as well as providing future perspectives for commercial utilization. The use of ureolytic bacteria in MICP demonstrates cost-efficiency, environmental compatibility, and successful pollutant abatement over tradition bioremediation techniques, and bio-synthesis of nanoparticles. limitations such as large-scale application, elevated Ca 2+ levels in groundwater, and gradual contaminant release need to be overcome. The possible future research directions for MICP technology, emphasizing its potential in conventional remediation, CO 2 sequestration, bio-material synthesis, and its role in reducing environmental impact for long-term economic benefits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Computed tomography aortic valve calcium (AVC) score has accepted value for diagnosing and predicting outcomes in aortic stenosis (AS). Multi-energy CT (MECT) allows virtual non-contrast (VNC) reconstructions from contrast scans. We aim to compare the VNC-AVC score to the true non-contrast (TNC)-AVC score for assessing AS severity., Methods: We prospectively included patients undergoing a MECT for transcatheter aortic valve replacement (TAVR) planning. TNC-AVC was acquired before contrast, and VNC-AVC was derived from a retrospectively gated contrast-enhanced scan. The Agatston scoring method was used for quantification, and linear regression analysis to derive adjusted-VNC values., Results: Among 109 patients (55% female) included, 43% had concordant severe and 14% concordant moderate AS. TNC scan median dose-length product was 116 ​mGy∗cm. The median TNC-AVC was 2,107 AU (1,093-3,372), while VNC-AVC was 1,835 AU (1293-2,972) after applying the coefficient (1.46) and constant (743) terms. A strong correlation was demonstrated between methods (r ​= ​0.93; p ​< ​0.001). Using accepted thresholds (>1,300 AU for women and >2,000 AU for men), 65% (n ​= ​71) of patients had severe AS by TNC-AVC and 67% (n ​= ​73) by adjusted-VNC-AVC. After estimating thresholds for adjusted-VNC (>1,564 AU for women and >2,375 AU for men), 56% (n ​= ​61) had severe AS, demonstrating substantial agreement with TNC-AVC (κ ​= ​0.77)., Conclusions: MECT-derived VNC-AVC showed a strong correlation with TNC-AVC. After adjustment, VNC-AVC demonstrated substantial agreement with TNC-AVC, potentially eliminating the requirement for an additional scan and enabling reductions in both radiation exposure and acquisition time., Competing Interests: Declaration of competing interest L.S. has received consulting honorarium from Amgen, BMS and Philips; and grant support from Amgen and Philips. D. L and P.P are supported by grants from Amgen and Philips. D.D. have received software royalties from Cedars-Sinai Medical Center. D.D. was supported by grants from National Heart, Lung and Blood institute (1R01HL133616 and 1R01HL148787-01A1). S.S.H. is an employee of Philips Healthcare. Other authors declare no conflict., (Copyright © 2023 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Nonalcoholic Fatty Liver Disease (NAFLD) is proving to be a globally prevalent condition. Moreover, NAFLD may be an independent risk factor associated with higher cardiovascular (CVD) morbidity and mortality. Further studies are needed to assess whether NAFLD needs to be included in the atherosclerotic risk score algorithms or whether patients with NAFLD need to be screened early on to assess their CVD risk especially since imaging such as positron emission tomography can be used to assess both NAFLD and CV disease at the same time. Therefore employing cardiovascular imaging modalities to investigate the incidence, extent, and nature of atherosclerotic lesions in NAFLD may be beneficial. Additionally, whether treating NAFLD halts the progression of CVD on imaging remains to be seen. Further research to delineate NAFLD and CVD associations, deciphering screening imaging modalities, and investigating targeted interventions could improve CVD morbidity and mortality in NAFLD., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors confirm that neither the manuscript nor any part of it was written or published or is under consideration for publication elsewhere., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Coronary artery disease is the leading cause of morbidity and mortality worldwide. Despite remarkable advances in the management of coronary artery disease, the prediction of adverse coronary events remains challenging. Over the preceding decades, considerable effort has been made to improve risk stratification using noninvasive imaging. Recently, these efforts have increasingly focused on the direct imaging of coronary atherosclerotic plaque. Modern imaging now allows imaging of coronary plaque burden, plaque type, atherosclerotic plaque activity, and plaque thrombosis, which have major potential to refine patient risk stratification, aid decision making, and advance future clinical practice., Competing Interests: Funding Support and Author Disclosures Dr Newby (CH/09/002, RE/18/5/34216, RG/16/10/32375), Dr Dweck (FS/14/78/31020), and Dr Williams (FS/11/014, CH/09/002, FS/ICRF/20/26002) are supported by the British Heart Foundation. Dr Tzolos was supported by a grant from Dr Miriam and the Sheldon G. Adelson Medical Research Foundation. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA) and Dr Dweck of the Sir Jules Thorn Award for Biomedical Research Award (2015). Dr Dey (R01HL133616) and Dr Slomka (R35HL161195) are supported by the National Heart, Lung, and Blood Institute/National Institute of Health (NHLBI/NIH)., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery disease reporting and data system (CAD-RADS) predicts future cardiovascular events in patients with coronary artery disease (CAD). However, information on vascular inflammation and vulnerability remains scarce., Methods: Patients who underwent coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) prior to coronary intervention were enrolled. All three coronary arteries were evaluated for CAD-RADS score and pericoronary adipose tissue (PCAT) attenuation, while the culprit vessel was analyzed for plaque vulnerability by OCT., Results: A total of 385 patients with 915 lesions were divided into two groups based on CAD-RADS score: 103 (26.8%) were categorized as CAD-RADS 4b/5 and 282 (73.2%) as CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had a higher level of PCAT attenuation (mean of 3 coronary arteries) than those with CAD-RADS ≤4a (-68.4 ​± ​6.7 HU vs. -70.1 ​± ​6.5, P ​= ​0.022). The prevalence of macrophage was higher, and lipid index was greater in patients with CAD-RADS 4b/5 than CAD-RADS ≤4a (94.2% vs. 83.0%, P ​= ​0.004, 1845 vs. 1477; P ​= ​0.003). These associations were significant in the culprit vessels of patients with chronic coronary syndrome but not in those with acute coronary syndromes., Conclusions: Higher CAD-RADS score was associated with higher levels of vascular inflammation and plaque vulnerability., Competing Interests: Declaration of competing interest Dr. Jang reports receiving educational grants from Abbott Vascular and consulting fees from Svelte Medical Systems, Inc. Dr. Ferencik has received consulting fees from Siemens Healthineers, HeartFlow, and Elucid. All other authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Extracellular volume (ECV) is a quantitative measure of extracellular compartment expansion, and an increase in ECV is a marker of myocardial fibrosis. Although cardiac magnetic resonance (CMR) is considered the standard imaging tool for ECV quantification, cardiac computed tomography (CT) has also been used for ECV assessment., Objectives: The aim of this meta-analysis was to evaluate the correlation and agreement in the quantification of myocardial ECV by CT and CMR., Methods: PubMed and Web of Science were searched for relevant publications reporting on the use of CT for ECV quantification compared with CMR as the reference standard. The authors employed a meta-analysis using the restricted maximum-likelihood estimator with a random-effects method to estimate summary correlation and mean difference. A subgroup analysis was performed to compare the correlation and mean differences between single-energy CT (SECT) and dual-energy CT (DECT) techniques for the ECV quantification., Results: Of 435 papers, 13 studies comprising 383 patients were identified. The mean age range was 57.3 to 82 years, and 65% of patients were male. Overall, there was an excellent correlation between CT-derived ECV and CMR-derived ECV (mean: 0.90 [95% CI: 0.86-0.95]). The pooled mean difference between CT and CMR was 0.96% (95% CI: 0.14%-1.78%). Seven studies reported correlation values using SECT, and 4 studies reported those using DECT. The pooled correlation from studies utilizing DECT for ECV quantification was significantly higher compared with those with SECT (mean: 0.94 [95% CI: 0.91-0.98] vs 0.87 [95% CI: 0.80-0.94], respectively; P = 0.01). There was no significant difference in pooled mean differences between SECT vs DECT (P = 0.85)., Conclusions: CT-derived ECV showed an excellent correlation and mean difference of <1% with CMR-derived ECV. However, the overall quality of the included studies was low, and larger, prospective studies are needed to examine the accuracy and diagnostic and prognostic utility of CT-derived ECV., Competing Interests: Funding Support and Author Disclosures This work was supported in part by the Dr Miriam and Sheldon G. Adelson Medical Research Foundation. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Artificial intelligence (AI) promises to revolutionize many fields, but its clinical implementation in cardiovascular imaging is still rare despite increasing research. We sought to facilitate discussion across several fields and across the lifecycle of research, development, validation, and implementation to identify challenges and opportunities to further translation of AI in cardiovascular imaging. Furthermore, it seemed apparent that a multidisciplinary effort across institutions would be essential to overcome these challenges. This paper summarizes the proceedings of the National Heart, Lung, and Blood Institute-led workshop, creating consensus around needs and opportunities for institutions at several levels to support and advance research in this field and support future translation., Competing Interests: Funding Support and Author Disclosures The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the official views of the National Heart, Lung, and Blood Institute, National Institutes of Health, or the United States Department of Health and Human Services. The National Heart, Lung, and Blood Institute (NHLBI) Workshop on Artificial Intelligence in Cardiovascular Imaging: Translating Science to Patient Care, held on June 27 and 28, 2022, was supported by the Division of Cardiovascular Sciences, NHLBI. Dr Antani has been supported by the Intramural Research Program of the National Library of Medicine and National Institutes of Health (NIH). Dr Arnaout has been supported by the NIH, the Department of Defense, and the Gordon and Betty Moore Foundation. Dr Dey has received software royalties from Cedars Sinai; and funding support from NIH/NHLBI grants (1R01HL148787-01A1 and 1R01HL151266). Dr Leiner has served on the Advisory Board for Cart-Tech B.V. and AI4Med; has been a clinical advisor for Quantib B.V.; has been a consultant for Guerbet; and has received funding support from the Netherlands Heart Foundation. Dr Sengupta has served on the Advisory Boards of Echo IQ and RCE Technologies; and has received funding support from NSF Award: 2125872 and NRT-HDR: Bridges in Digital Health. Dr Shah has received consulting fees from AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer-Ingelheim, Boston Scientific, Bristol Myers Squib, Cytokinetics, Edwards Lifesciences, Eidos, Gordian, Intellia, Ionis, Merck, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and United Therapeutics; and has received funding support from the NIH (U54 HL160273, R01 HL140731, R01 HL149423), Corvia, and Pfizer. Dr Slomka has received software royalties from Cedars Sinai; and has received funding support from the NIH/NHLBI grant 1R35HL161195-01. Dr Williams has been a speaker at lectures sponsored by Canon Medical Systems and the Siemens Healthineers; and has received funding support from the British Heart Foundation (FS/ICRF/20/26002). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Coronary inflammation is postulated as a driver of atherosclerosis and dysfunctional arterial healing which may trigger stent failure. Pericoronary adipose tissue (PCAT) attenuation, detected on computer tomography coronary angiography (CTCA), is an emerging non-invasive marker of coronary inflammation. This propensity matched study assessed the utility of both lesion specific (PCAT Lesion ) and standardized PCAT attenuation as assessed in the proximal RCA (PCAT RCA ) as a predictor of stent failure in patients undergoing elective percutaneous coronary intervention. This is the first study to our knowledge that assesses the association of PCAT with stent failure., Methods: Patients undergoing CTCA assessment for coronary artery disease with subsequent stent insertion within 60 days and repeat coronary angiography for any clinical reason within 5 years were included in the study. Stent failure was defined as binary restenosis of >50 % on quantitative coronary angiography analysis or stent thrombosis. Both PCAT Lesion and PCAT RCA was assessed utilizing semi-automated proprietary software on baseline CTCA. Patients with stent failure were propensity matched utilizing age, sex, cardiovascular risk factors and procedural characteristics., Results: One hundred and fifty-one patients met inclusion criteria. Of these, 26 (17.2 %) had study-defined failure. A significant difference in PCAT Lesion attenuation between patients with and without failure was observed (-79.0 ± 12.6 vs. -85.9 ± 10.3HU, p = 0.035). There was no significant difference in PCAT RCA attenuation between the two groups (-79.5 ± 10.1 vs -81.0 ± 12.3HU, p = 0.50). Univariate regression analysis showed PCAT Lesion attenuation was independently associated with stent failure (OR 1.06, 95 % CI 1.01-1.12, P = 0.035)., Conclusions: Patients with stent failure exhibit significantly increased PCAT Lesion attenuation at baseline. These data suggest that baseline plaque inflammation may be an important driver for coronary stent failure., Competing Interests: Conflict of interest All authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The diagnosis and management of myocardial infarction are increasingly complex, and establishing the presence of intracoronary thrombosis has major implications for both the classification and treatment of myocardial infarction., Objectives: The aim of this study was to investigate whether positron emission tomographic (PET) and computed tomographic (CT) imaging could noninvasively detect in vivo thrombus formation in human coronary arteries using a novel glycoprotein IIb/IIIa receptor antagonist-based radiotracer, 18 F-GP1., Methods: In a single-center observational case-control study, patients with or without acute myocardial infarction underwent coronary 18 F-GP1 PET/CT angiography. Coronary artery 18 F-GP1 uptake was assessed visually and quantified using maximum target-to-background ratios., Results: 18 F-GP1 PET/CT angiography was performed in 49 patients with and 50 patients without acute myocardial infarction (mean age: 61 ± 9 years, 75% men). Coronary 18 F-GP1 uptake was apparent in 39 of the 49 culprit lesions (80%) in patients with acute myocardial infarction. False negative results appeared to relate to time delays to scan performance and low thrombus burden in small-caliber distal arteries. On multivariable regression analysis, culprit vessel status was the only independent variable associated with higher 18 F-GP1 uptake. Extracoronary cardiac 18 F-GP1 findings included a high frequency of infarct-related intramyocardial uptake (35%) as well as left ventricular (8%) or left atrial (2%) thrombus., Conclusions: Coronary 18 F-GP1 PET/CT angiography is the first noninvasive selective technique to identify in vivo coronary thrombosis in patients with acute myocardial infarction. This novel approach can further define the role and location of thrombosis within the heart and has the potential to inform the diagnosis, management, and treatment of patients with acute myocardial infarction. (In-Vivo Thrombus Imaging With 18 F-GP1, a Novel Platelet PET Radiotracer [iThrombus]; NCT03943966)., Competing Interests: Funding Support and Author Disclosures The Edinburgh Clinical Research Facilities and Edinburgh Imaging facility is supported by the National Health Service Research Scotland through the National Health Service Lothian Health Board. This work was supported by several grant funding organizations. Drs Tzolos (FS/CRTF/20/24086), Williams (FS/ICRF/20/26002, FS/11/014, and CH/09/002), Newby (CH/09/002, RG/16/10/32375, and RE/18/5/34216), and Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr van Beek is supported by the Scottish Imaging Network: A Platform of Scientific Excellence. Dr Mills is supported by the British Heart Foundation through the award of Personal Chair and a Programme Grant (CH/F/21/90010 and RG/20/10/34966). Dr Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). Dr Slomka and FusionQuant analysis tools are supported by National Heart, Lung, and Blood Institute grant 5R01HL135557. Dr Dey and Autoplaque analysis tools are supported by National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1. Drs Koglin and Stephens are employees of Life Molecular Imaging, which provided reagents for radiotracer production. Dr Williams is a member of the Speakers Bureau for Canon Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Assessment of coronary artery calcium (CAC) by computed tomographic (CT) imaging provides an accurate measure of atherosclerotic burden. CAC is also visible in computed tomographic attenuation correction (CTAC) scans, always acquired with cardiac positron emission tomographic (PET) imaging., Objectives: The aim of this study was to develop a deep-learning (DL) model capable of fully automated CAC definition from PET CTAC scans., Methods: The novel DL model, originally developed for video applications, was adapted to rapidly quantify CAC. The model was trained using 9,543 expert-annotated CT scans and was tested in 4,331 patients from an external cohort undergoing PET/CT imaging with major adverse cardiac events (MACEs) (follow-up 4.3 years), including same-day paired electrocardiographically gated CAC scans available in 2,737 patients. MACE risk stratification in 4 CAC score categories (0, 1-100, 101-400, and >400) was analyzed and CAC scores derived from electrocardiographically gated CT scans (standard scores) by expert observers were compared with automatic DL scores from CTAC scans., Results: Automatic DL scoring required <6 seconds per scan. DL CTAC scores provided stepwise increase in the risk for MACE across the CAC score categories (HR up to 3.2; P < 0.001). Net reclassification improvement of standard CAC scores over DL CTAC scores was nonsignificant (-0.02; 95% CI: -0.11 to 0.07). The negative predictive values for MACE of zero CAC with standard (85%) and DL CTAC (83%) CAC scores were similar (P = 0.19)., Conclusions: DL CTAC scores predict cardiovascular risk similarly to standard CAC scores quantified manually by experienced operators from dedicated electrocardiographically gated CAC scans and can be obtained almost instantly, with no changes to PET/CT scanning protocol., Competing Interests: Funding Support and Author Disclosures This research was supported in part by grant R01HL089765 from the National Heart, Lung, and Blood Institute/National Institutes of Health (principal investigator, Piotr Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Pieszko was supported by a research scholarship from the Polish National Agency for Academic Exchange. Cedars-Sinai has a pending patent application on the use of convolutional long short-term memory for multislice medical image segmentation. Drs Berman, Slomka, and Van Kriekinge and Mr Kavanagh participate in software royalties for nuclear cardiology software at Cedars-Sinai Medical Center. Dr Slomka has received research grant support from Siemens Medical Systems. Dr Berman has served as a consultant for GE Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Distinct sex-related differences exist in coronary artery plaque burden and distribution. We aimed to explore sex differences in quantitative plaque burden by coronary CT angiography (CCTA) in relation to ischemia by invasive fractional flow reserve (FFR)., Methods: This post-hoc analysis of the PACIFIC trial included 581 vessels in 203 patients (mean age 58.1 ​± ​8.7 years, 63.5% male) who underwent CCTA and per-vessel invasive FFR. Quantitative assessment of total, calcified, non-calcified, and low-density non-calcified plaque burden were performed using semiautomated software. Significant ischemia was defined as invasive FFR ≤0.8., Results: The per-vessel frequency of ischemia was higher in men than women (33.5% vs. 7.5%, p ​< ​0.001). Women had a smaller burden of all plaque subtypes (all p ​< ​0.01). There was no sex difference on total, calcified, or non-calcified plaque burdens in vessels with ischemia; only low-density non-calcified plaque burden was significantly lower in women (beta: -0.183, p ​= ​0.035). The burdens of all plaque subtypes were independently associated with ischemia in both men and women (For total plaque burden (5% increase): Men, OR: 1.15, 95%CI: 1.06-1.24, p ​= ​0.001; Women, OR: 1.96, 95%CI: 1.11-3.46, p ​= ​0.02). No significant interaction existed between sex and total plaque burden for predicting ischemia (interaction p ​= ​0.108). The addition of quantitative plaque burdens to stenosis severity and adverse plaque characteristics improved the discrimination of ischemia in both men and women., Conclusions: In symptomatic patients with suspected CAD, women have a lower CCTA-derived burden of all plaque subtypes compared to men. Quantitative plaque burden provides independent and incremental predictive value for ischemia, irrespective of sex., Competing Interests: Declaration of Competing Interest Outside of the current work, S.C., P.S., and D.D. received software royalties from Cedars-Sinai Medical Center. D.B, P.S., and D.D. hold a patent (US8885905B2 in USA and WO patent WO2011069120A1, Method and System for Plaque Characterization)., (Copyright © 2022 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial perfusion imaging (MPI) is frequently used to provide risk stratification, but methods to improve the accuracy of these predictions are needed., Objectives: The authors developed an explainable deep learning (DL) model (HARD MACE [major adverse cardiac events]-DL) for the prediction of death or nonfatal myocardial infarction (MI) and validated its performance in large internal and external testing groups., Methods: Patients undergoing single-photon emission computed tomography MPI were included, with 20,401 patients in the training and internal testing group (5 sites) and 9,019 in the external testing group (2 different sites). HARD MACE-DL uses myocardial perfusion, motion, thickening, and phase polar maps combined with age, sex, and cardiac volumes. The primary outcome was all-cause mortality or nonfatal MI. Prognostic accuracy was evaluated using area under the receiver-operating characteristic curve (AUC)., Results: During internal testing, patients with normal perfusion and elevated HARD MACE-DL risk were at higher risk than patients with abnormal perfusion and low HARD MACE-DL risk (annualized event rate, 2.9% vs 1.2%; P < 0.001). Patients in the highest quartile of HARD MACE-DL score had an annual rate of death or MI (4.8%) 10-fold higher than patients in the lowest quartile (0.48% per year). In external testing, the AUC for HARD MACE-DL (0.73; 95% CI: 0.71-0.75) was higher than a logistic regression model (AUC: 0.70), stress total perfusion deficit (TPD) (AUC: 0.65), and ischemic TPD (AUC: 0.63; all P < 0.01). Calibration, a measure of how well predicted risk matches actual risk, was excellent in both groups (Brier score, 0.079 for internal and 0.070 for external)., Conclusions: The DL model predicts death or MI directly from MPI, by estimating patient-level risk with good calibration and improved accuracy compared with traditional quantitative approaches. The model incorporates mechanisms to explain to the physician which image regions contribute to the adverse event prediction., Competing Interests: Funding Support and Author Disclosures This research (principal investigator: Dr Slomka) was supported in part by grant R01HL089765 from the National Heart, Lung and Blood Institute of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mr Kavanagh has participated in software royalties for QPS software at Cedars-Sinai Medical Center. Dr Einstein has served as a consultant to GE Healthcare and W.L. Gore & Associates; and his institution has received research support from GE Healthcare, Philips Healthcare, Toshiba America Medical Systems, Roche Medical Systems, and W.L. Gore & Associates. Dr Ruddy has received research grant support from GE Healthcare and Advanced Accelerator Applications. Dr Edward Miller has served as a consultant to GE Healthcare. Dr Dorbala has served as a consultant to GE Healthcare and Bracco Diagnostics; and her institution has received grant support from Astellas. Dr Di Carli has received research grant support from Spectrum Dynamics; and has received consulting honoraria from Sanofi and GE Healthcare. Dr Berman has participated in software royalties for QPS software at Cedars-Sinai Medical Center; and has served as a consultant to GE Healthcare. Dr Slomka has participated in software royalties for QPS software at Cedars-Sinai Medical Center; and has received research grant support from Siemens Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary CT angiography (CCTA) pericoronary adipose tissue (PCAT) markers are promising indicators of inflammation., Objective: To determine the effect of patient and imaging parameters on the associations between non-calcified plaque (NCP) and PCAT attenuation and gradient., Methods: This was a single-center, retrospective analysis of consecutive patients with stable chest pain who underwent CCTA and had zero calcium scores. CCTA images were evaluated for the presence of NCP, obstructive stenosis, segment stenosis and involvement score (SSS, SIS), and high-risk plaque (HRP). PCAT markers were assessed using semi-automated software. Uni- and multivariable regression models correcting for patient and imaging characteristics between plaque and PCAT markers were evaluated., Results: Overall, 1652 patients had zero calcium score (mean age: 51 years ​± ​11 [SD], 871 women); PCAT attenuation values ranged between -123 HU and -51 HU, and 649 patients had plaque. In univariable analysis, the presence of NCP, SSS, SIS, and HRP were associated with PCAT attenuation (2, 1, 1, 6 HU; respectively; p ​< ​.001 all); while obstructive stenosis was not (1 HU, p ​= ​.58). In multivariable analysis, none of the plaque markers were associated with PCAT attenuation (0 HU p ​= ​.93, 0 HU p ​= ​.39, 1 HU p ​= ​.18, 2 HU p ​= ​.10, 1 HU p ​= ​.71, respectively), while patient and imaging characteristics showed significant associations, such as: male sex (1 HU, p ​= ​.003), heart rate [1/min] (-0.2 HU, p ​< ​.001), 120 ​kVp (8 HU, p ​< ​.001) and pixel spacing [mm 3 ] (32 HU, p ​< ​.001). Similar results were observed for PCAT gradient., Conclusion: PCAT markers were significantly associated with NCP, however the associations did not persist following correction for patient and imaging characteristics., Competing Interests: Conflicts of interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In patients with stable chest pain, computed tomography (CT) plaque burden is an independent predictor of future coronary events., Objectives: The purpose of this study was to determine whether plaque burden and characteristics can predict subsequent death or myocardial infarction in patients with acute chest pain., Methods: In a post hoc analysis of a multicenter trial of early coronary CT angiography, the authors performed quantitative plaque analysis to assess the association between primary endpoint of 1-year all-cause death or nonfatal myocardial infarction and the GRACE (Global Registry of Acute Coronary Events) score, presence of obstructive coronary artery disease, and plaque burden in 404 patients with suspected acute coronary syndrome., Results: Following the index event, 25 patients had a primary event that was associated with a higher GRACE score (134 ± 44 vs 113 ± 35; P = 0.012), larger burdens of total (46% [IQR: 43%-50%] vs 36% [IQR: 21%-46%]; P < 0.001), noncalcified (41% [IQR: 37%-%47] vs 33% [IQR: 20%-41%]; P < 0.001), and low-attenuation plaque (4.22% [IQR: 3.3%-5.68%] vs 2.14% [IQR: 0.5%-4.88%]; P < 0.001), but not obstructive coronary artery disease (P = 0.065). Total, noncalcified, and low-attenuation plaque burden were the strongest predictors of future events independent of GRACE score and obstructive coronary artery disease (P ≤ 0.002 for all). Patients with a low-attenuation burden above the median had nearly an 8-fold increased risk of the primary endpoint (HR: 7.80 [95% CI: 2.33-26.0]; P < 0.001), outperforming either a GRACE score of >140 (HR: 3.80 [95% CI :1.45-6.98]; P = 0.004) or obstructive coronary artery disease (HR: 2.07 [95% CI: 0.94-4.53]; P = 0.07)., Conclusions: In patients with suspected acute coronary syndrome, low-attenuation plaque burden is a major predictor of 1-year death or recurrent myocardial infarction. (Rapid Assessment of Potential Ischaemic Heart Disease With CTCA [RAPID-CTCA]; NCT02284191)., Competing Interests: Funding Support and Author Disclosures The National Institute for Health Research HTA Programme funded the RAPID-CTCA trial study (13/04/108). Dr Meah is supported by the British Heart Foundation (FS/19/46/34445). Dr Tzolos is supported by a British Heart Foundation grant (FS/CRTF/20/24086). Dr Bularga is supported by a clinical research training fellowship (MR/V007254/1). Dr Curzen has received unrestricted research grants from Boston Scientific, HeartFlow, and Beckmann Coulter. Drs Mills, Newby, and Williams are supported by the British Heart Foundation (FS/ICRF/20/26002, CH/09/002, RG/20/10/34966, RE/18/5/34216, CH/F/21/90010). Drs Slomka and Dey have received software royalties from Cedars-Sinai Medical Center and have a patent, outside of the current study. Dr Dey is supported by National Institute of Health/National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1 and 1R01HL151266. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Ovarian cancer is one of the deadliest gynecological cancers and the 7th most commonly occurring cancer in women globally. The 5 year survival rate is estimated to be less than 25 %, as in most cases, diagnosis occurs at an advanced stage. Despite recent advancements in treatment, clinical outcomes still remain poor, thus implicating the need for urgent identification of novel therapeutics for the treatment of this cancer. Ovarian cancer is considered a low immune reactive cancer as the tumor cells express insufficient neoantigens to be recognized by the immune cells and thus tend to escape from immune surveillance. Thus, in the recent decade, immunotherapy has gained significant attention and has rejuvenated the understanding of immune regulation in tumor biology. One of the critical immune checkpoints is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis. Engagement of PD-1 to PD-L1 promotes immunologic tolerance and suppresses the effector T cells and maintains tumor Tregs, thus playing a crucial role in enhancing tumor survival. Recent studies are targeted to develop inhibitors that block this signal to augment the anti-tumor activity of immune cells. Also, compared to monotherapy, the combinatorial treatment of immune checkpoint inhibitors with small molecule inhibitors have shown promising results with improved efficacy and acceptable adverse events. The present review provides an overview of the PD-1/PD-L1 axis and role of non-coding RNAs in regulating this axis. Moreover, we have highlighted the various preclinical and clinical investigations on PD-1/PD-L1 immune checkpoint inhibitors and have discussed the limitations of immunotherapies in ovarian cancer., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Mammographically detected breast arterial calcification (BAC) has been proposed as surrogate marker for coronary artery disease (CAD) in women. Epicardial adipose tissue (EAT) and peri-coronary adipose tissue (PCAT) are inflammatory fat depots linked to atherogenesis. BAC has demonstrated association with inflammation, therefore we aimed to determine the association between BAC, EAT and PCAT., Methods: Single-centre, retrospective, cross-sectional study of women with digital mammography and coronary computed tomography angiography (CCTA). EAT and PCAT were quantitively assessed using semi-automated software. Patient demographics and cardiovascular risk factors were obtained from medical records and mammograms reviewed for BAC. Pre-test cardiovascular risk was determined with CAD Consortium Score. Chi-square, t-test and Mann-Whitney U tests were used to assess between group differences. Multivariable linear and logistic regression modelling was conducted to adjust for confounders., Results: Among 153 patients (age 61, SD 11) included in this study, BAC was present in 37 (24%) patients. BAC-positive patients had higher EAT volume (EATv) (110.2 mL, SD 41 mL vs 94.4 mL, SD 41 mL, p = 0.02) but this association was not significant after adjusting for cardiovascular risk factors (p = 0.26). BAC did not associate with EAT density or PCAT. BAC and EATv were strongly associated with cardiovascular risk and CAD independent of each other: CV risk (BAC OR 7.55 (3.26-18.49), p < 0.001, EATv OR 1.02 (1.01-1.03), p < 0.001), CAD presence (BAC OR 4.26 (1.39-13), p = 0.01; EATv OR 1.01 (1.0-1.03), p = 0.04)., Conclusion: BAC and EATv are independent predictors of CV risk and CAD, but don't independently associate with each other, the relationship confounded by shared cardiovascular risk factors. BAC doesn't appear to associate with adipose tissue density and its presence may be cumulative result of long-term exposure to CV risk factors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Machine learning (ML) models can improve prediction of major adverse cardiovascular events (MACE), but in clinical practice some values may be missing. We evaluated the influence of missing values in ML models for patient-specific prediction of MACE risk., Methods: We included 20,179 patients from the multicenter REFINE SPECT registry with MACE follow-up data. We evaluated seven methods for handling missing values: 1) removal of variables with missing values (ML-Remove), 2) imputation with median and unique category for continuous and categorical variables, respectively (ML-Traditional), 3) unique category for missing variables (ML-Unique), 4) cluster-based imputation (ML-Cluster), 5) regression-based imputation (ML-Regression), 6) missRanger imputation (ML-MR), and 7) multiple imputation (ML-MICE). We trained ML models with full data and simulated missing values in testing patients. Prediction performance was evaluated using area under the receiver-operating characteristic curve (AUC) and compared with a model without missing values (ML-All), expert visual diagnosis and total perfusion deficit (TPD)., Results: During mean follow-up of 4.7 ± 1.5 years, 3,541 patients experienced at least one MACE (3.7% annualized risk). ML-All (reference model-no missing values) had AUC 0.799 for MACE risk prediction. All seven models with missing values had lower AUC (ML-Remove: 0.778, ML-MICE: 0.774, ML-Cluster: 0.771, ML-Traditional: 0.771, ML-Regression: 0.770, ML-MR: 0.766, and ML-Unique: 0.766; p < 0.01 for ML-Remove vs remaining methods). Stress TPD (AUC 0.698) and visual diagnosis (0.681) had the lowest AUCs., Conclusion: Missing values reduce the accuracy of ML models when predicting MACE risk. Removing variables with missing values and retraining the model may yield superior patient-level prediction performance., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Enteric fever caused by Salmonella enterica serovar typhi and Salmonella enterica serovar paratyphi A remains one of the most common causes of community-acquired bloodstream infection among children in India. Multidrug resistance is emerging and is a cause of concern as it affects the choice of treatment in enteric fever., Method: In this study, a 10-year analysis of resistance patterns was done along with in-silico homology modeling and molecular docking to understand the commonly occurring quinolone resistance., Results: A total of 1010 cases of blood culture-confirmed enteric fevers (S. typhi n=849; S. paratyphi A n=161) were recorded at the study hospital during the period from 2011-2020. Multidrug resistance among cases of S. typhi was 2.12 %, whereas it was completely absent among cases of S. paratyphi A. Fluoroquinolone resistance was high (>95%) throughout the study period. Resistance to ampicillin, chloramphenicol and co-trimoxacole was low (<3%) among S. typhi cases. No deaths were observed among study participants. Molecular docking analysis showed that quinolone had less binding affinity to mutated gyrase A than to its wild type for both S. typhi and S. paratyphi A., Conclusion: Quinolone resistance was high among cases of enteric fever, whereas no resistance was observed among third-generation cephalosporins. In-silico studies indicated that a mutation in gyrase A might be the cause of the gradual increase in ciprofloxacin resistance over the study period., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Various pro- and anti-inflammatory biomarkers are involved in the process of atherosclerosis. We analyzed the association of different biomarkers with coronary plaque volume and vulnerable plaque subcomponents., Methods: In 301 patients undergoing coronary CT angiography (CTA), total coronary plaque volume (TPV) and subcomponents including non-calcified plaque volume (NCPV) and vulnerable plaque burden were quantified using semi-automated software. Serum was analyzed for various cytokines., Results: Out of 301 patients, 207 (69%) were male. The mean age was 59 ± 10 years. Patients were divided using the median of TPV, NCPV and vulnerable plaque burden. In univariable analysis, patients with high TPV, high NCPV and high vulnerable plaque burden showed significant higher serum levels for IFNƔ, IL-1a, -2, -4, -10 and -17 and significant lower levels for IL-8 and MCP-1 (all p < 0.05). Multivariable analysis showed positive associations between high vulnerable plaque burden, IL-1a (OR 2.60, p = 0.001) and Eotaxin (OR 1.89, p = 0.020), and inverse association to MCP-1 (OR 0.33, p < 0.001), independent of age, gender and CVRF. In exploratory subanalyses, patients with presence of atherosclerosis (n = 247; 82%) showed significantly higher levels of IL-17 in all subgroups with high vulnerable plaque burden, irrespective of overall plaque volume (all p < 0.001)., Conclusions: The cytokine profile significantly differs between patients with high and low coronary plaque volume. IL-1a and IL-17 seem to play a major proatherogenic role in vulnerable plaque formation, whereas MCP-1 paradoxically portends protective effects. Longitudinal studies with serial cytokine testing are needed to identify potential targets for therapeutic interventions., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Explainable artificial intelligence (AI) can be integrated within standard clinical software to facilitate the acceptance of the diagnostic findings during clinical interpretation., Objectives: This study sought to develop and evaluate a novel, general purpose, explainable deep learning model (coronary artery disease-deep learning [CAD-DL]) for the detection of obstructive CAD following single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)., Methods: A total of 3,578 patients with suspected CAD undergoing SPECT MPI and invasive coronary angiography within a 6-month interval from 9 centers were studied. CAD-DL computes the probability of obstructive CAD from stress myocardial perfusion, wall motion, and wall thickening maps, as well as left ventricular volumes, age, and sex. Myocardial regions contributing to the CAD-DL prediction are highlighted to explain the findings to the physician. A clinical prototype was integrated using a standard clinical workstation. Diagnostic performance by CAD-DL was compared to automated quantitative total perfusion deficit (TPD) and reader diagnosis., Results: In total, 2,247 patients (63%) had obstructive CAD. In 10-fold repeated testing, the area under the receiver-operating characteristic curve (AUC) (95% CI) was higher according to CAD-DL (AUC: 0.83 [95% CI: 0.82-0.85]) than stress TPD (AUC: 0.78 [95% CI: 0.77-0.80]) or reader diagnosis (AUC: 0.71 [95% CI: 0.69-0.72]; P < 0.0001 for both). In external testing, the AUC in 555 patients was higher according to CAD-DL (AUC: 0.80 [95% CI: 0.76-0.84]) than stress TPD (AUC: 0.73 [95% CI: 0.69-0.77]) or reader diagnosis (AUC: 0.65 [95% CI: 0.61-0.69]; P < 0.001 for all). The present model can be integrated within standard clinical software and generates results rapidly (<12 seconds on a standard clinical workstation) and therefore could readily be incorporated into a typical clinical workflow., Conclusions: The deep-learning model significantly surpasses the diagnostic accuracy of standard quantitative analysis and clinical visual reading for MPI. Explainable artificial intelligence can be integrated within standard clinical software to facilitate acceptance of artificial intelligence diagnosis of CAD following MPI., Competing Interests: Funding Support and Author Disclosures This research was supported in part by National Heart, Lung, and Blood Institute/National Institutes of Health grant R01HL089765 (principal investigator: Piotr Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Drs Berman and Slomka and Mr Kavanagh participated in software royalties for QPS software at Cedars-Sinai Medical Center. Dr Slomka has received research grant support from Siemens Medical Systems. Drs Berman, Dorbala, Einstein, and Edward Miller are consultants for GE Healthcare. Dr Einstein is a consultant for W.L. Gore & Associates. Dr Dorbala is a consultant for Bracco Diagnostics; and has received a grant through her institution from Astellas. Dr Di Carli has received research grant support from Spectrum Dynamics; and he is a consultant for Sanofi and GE Healthcare. Dr Ruddy has received research grant support from GE Healthcare and Advanced Accelerator Applications. Dr Einstein has received research support through his institution from GE Healthcare, Philips Healthcare, Toshiba America Medical Systems, Roche Medical Systems, and W.L. Gore & Associates. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Bioprosthetic valve thrombosis may have implications for valve function and durability., Objectives: Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves., Methods: Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT., Results: Flow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake., Conclusions: Adherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875)., Competing Interests: Funding Support and Author Disclosures This work was funded by the British Heart Foundation, London, United Kingdom (RG/16/10/32375 and PG/19/40/34422). The Edinburgh Clinical Research Facilities and Edinburgh Imaging facility is supported by the National Health Service Research Scotland (NRS) through National Health Service Lothian Health Board. This work and Drs Bing, Tzolos, Williams, Dweck, and Newby are supported by the British Heart Foundation (PG/19/40/34422, FS/ICRF/20/26002, FS/CRTF/20/24086, FS/14/78/31020, CH/09/002, RG/16/10/32375, RE/18/5/34216, FS/SCRF/21/32010). Dr van Beek is supported by the Scottish Imaging Network. Dr Sellers is supported by fellowships from the Michael Smith Foundation for Health Research and the Canadian Institutes of Health Research. Drs Koglin and Stephens are employees of Life Molecular Imaging GmbH, who provided reagents for radiotracer production. Dr Leipsic is supported by a Canadian Research Chair in Advanced CardioPulmonary Imaging and the Jon DeHaan Award for Innovation in Cardiology; is a consultant for Edward Lifesciences; and provides computed tomography core laboratory services to Edwards Lifesciences, Medtronic, Neovasc, Aegis, and Tendyne, for which no direct compensation is received. Dr Williams is supported by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (PCL/17/04). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Pericoronary adipose tissue (PCAT) attenuation and low-attenuation noncalcified plaque (LAP) burden can both predict outcomes., Objectives: This study sought to assess the relative and additive values of PCAT attenuation and LAP to predict future risk of myocardial infarction., Methods: In a post hoc analysis of the multicenter SCOT-HEART (Scottish Computed Tomography of the Heart) trial, the authors investigated the relationships between the future risk of fatal or nonfatal myocardial infarction and PCAT attenuation measured from coronary computed tomography angiography (CTA) using multivariable Cox regression models including plaque burden, obstructive coronary disease, and cardiac risk score (incorporating age, sex, diabetes, smoking, hypertension, hyperlipidemia, and family history)., Results: In 1,697 evaluable participants (age: 58 ± 10 years), there were 37 myocardial infarctions after a median follow-up of 4.7 years. Mean PCAT was -76 ± 8 HU and median LAP burden was 4.20% (IQR: 0%-6.86%). PCAT attenuation of the right coronary artery (RCA) was predictive of myocardial infarction (HR: 1.55; P = 0.017, per 1 SD increment) with an optimum threshold of -70.5 HU (HR: 2.45; P = 0.01). In multivariable analysis, adding PCAT-RCA of ≥-70.5 HU to an LAP burden of >4% (the optimum threshold for future myocardial infarction; HR: 4.87; P < 0.0001) led to improved prediction of future myocardial infarction (HR: 11.7; P < 0.0001). LAP burden showed higher area under the curve compared to PCAT attenuation for the prediction of myocardial infarction (AUC = 0.71 [95% CI: 0.62-0.80] vs AUC = 0.64 [95% CI: 0.54-0.74]; P < 0.001), with increased area under the curve when the 2 metrics are combined (AUC = 0.75 [95% CI: 0.65-0.85]; P = 0.037)., Conclusion: Coronary CTA-defined LAP burden and PCAT attenuation have marked and complementary predictive value for the risk of fatal or nonfatal myocardial infarction., Competing Interests: Funding Support and Author Disclosures This trial was funded by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (CZH/4/588), with supplementary awards from Edinburgh and Lothian’s Health Foundation Trust and the Heart Diseases Research Fund. Dr Williams, (FS/ICRF/20/26002, FS/11/014, CH/09/002), Dr Newby (CH/09/002, RG/16/10/32375, RE/18/5/34216), and Dr Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Williams was supported by The Chief Scientist Office of the Scottish Government Health (PCL/17/04). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr van Beek is supported by the Scottish Imaging Network: A Platform of Scientific Excellence (SINAPSE). Dr Mills is supported by the British Heart Foundation through the award of the Butler Senior Clinical Research Fellowship and a Programme Grant (FS/16/14/32023, RG/20/10/34966). Dr Adamson is supported by a National Heart Foundation of New Zealand Senior Fellowship (1844). Dr Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). The Royal Bank of Scotland supported the provision of the 320-multidetector computed tomography for National Health Service Lothian and the University of Edinburgh. The Edinburgh Imaging Facility, The Queen's Medical Research Institute (Edinburgh) is supported by the National Health Service Research Scotland through the National Health Service Lothian Health Board. The Clinical Research Facility Glasgow and Clinical Research Facility Tayside are supported by National Health Service Research Scotland. This work is supported in part by the National Institutes of Health/National Heart, Lung, and Blood Institute grants 1R01HL148787-01A1 and 1R01HL151266. Drs Lin and Grodecki, Priscilla McElhinney, Sebastien Cadet, and Dr Dey are supported by National Institutes of Health/National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1. This work is also supported in part by the Miriam and Sheldon G. Adelson Medical Research Foundation. Sebastien Cadet, and Drs Berman, Slomka, and Dey received software royalties from Cedars-Sinai Medical Center. Drs Slomka, Berman, and Dey hold a patent (US8885905B2 in the United States and World Intellectual Property Organization patent WO2011069120A1, “Method and System for Plaque Characterization”). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Chronic diseases are considered a major public health concern worldwide, and most of these diseases like cancer, cardiovascular, metabolic, and neurological disorders occur due to atypical regulation of multiple signaling pathways. It has also been observed that most of the currently approved therapies for these diseases fail to show prolonged efficacy due to their mono-targeted nature and are associated with the development of chemoresistance, thus restricting their utility. The plant-derived compounds, on the other hand, show multi-targeted nature, and thus these phytochemicals have gained wide attention as they offer negligible side effects. The present review aims to recapitulate the potential effects of one such phytochemical, Scopoletin, which was found to have a diverse range of pharmacological activities such as anti-cancer, anti-diabetic, anti-inflammatory, cardioprotective, hepatoprotective, etc. Scopoletin modulated multiple molecular signatures in cancer, including AMPK, EGFR, MAPK/ ERK, NF-κB, PI3K/Akt/ mTOR, and STAT3; regulated the levels of critical markers of metabolic diseases such as ALT, AST, TG, and TC; inflammatory diseases such as ILs and TNFs; neurological diseases such as AChE, etc. thus relieving the symptoms and severity associated with these diseases. Further, this compound has a non-toxic nature and possesses an excellent pharmacokinetic property, which warrants further investigation in clinical settings for developing it as a potential drug., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to precisely phenotype culprit and nonculprit lesions in myocardial infarction (MI) and lesions in stable coronary artery disease (CAD) using coronary computed tomography angiography (CTA)-based radiomic analysis., Background: It remains debated whether any single coronary atherosclerotic plaque within the vulnerable patient exhibits unique morphology conferring an increased risk of clinical events., Methods: A total of 60 patients with acute MI prospectively underwent coronary CTA before invasive angiography and were matched to 60 patients with stable CAD. For all coronary lesions, high-risk plaque (HRP) characteristics were qualitatively assessed, followed by semiautomated plaque quantification and extraction of 1,103 radiomic features. Machine learning models were built to examine the additive value of radiomic features for discriminating culprit lesions over and above HRP and plaque volumes., Results: Culprit lesions had higher mean volumes of noncalcified plaque (NCP) and low-density noncalcified plaque (LDNCP) compared with the highest-grade stenosis nonculprits and highest-grade stenosis stable CAD lesions (NCP: 138.1 mm 3 vs 110.7 mm 3 vs 102.7 mm 3 ; LDNCP: 14.2 mm 3 vs 9.8 mm 3 vs 8.4 mm 3 ; both P trend  < 0.01). In multivariable linear regression adjusted for NCP and LDNCP volumes, 14.9% (164 of 1,103) of radiomic features were associated with culprits and 9.7% (107 of 1,103) were associated with the highest-grade stenosis nonculprits (critical P < 0.0007) when compared with highest-grade stenosis stable CAD lesions as reference. Hierarchical clustering of significant radiomic features identified 9 unique data clusters (latent phenotypes): 5 contained radiomic features specific to culprits, 1 contained features specific to highest-grade stenosis nonculprits, and 3 contained features associated with either lesion type. Radiomic features provided incremental value for discriminating culprit lesions when added to a machine learning model containing HRP and plaque volumes (area under the receiver-operating characteristic curve 0.86 vs 0.76; P = 0.004)., Conclusions: Culprit lesions and highest-grade stenosis nonculprit lesions in MI have distinct radiomic signatures compared with lesions in stable CAD. Within the vulnerable patient may exist individual vulnerable plaques identifiable by coronary CTA-based precision phenotyping., Competing Interests: Funding Support and Author Disclosures This study was supported in part by grants from the National Heart, Lung, and Blood Institute (1R01HL133616 and 1R01HL148787-01A1). Outside of the current work, Drs Cadet, Slomka, and Dey have received software royalties from Cedars-Sinai Medical Center. Drs Slomka and Dey hold a patent (US8885905B2 in USA and WO patent WO2011069120A1, Method and System for Plaque Characterization). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare the level of coronary inflammation between plaque rupture and plaque erosion using pericoronary adipose tissue (PCAT) attenuation., Background: Vascular inflammation plays a key role in plaque rupture, while the role of inflammation in plaque erosion remains less well defined. PCAT attenuation determined using computed tomography has emerged as a marker specific for coronary artery inflammation., Methods: Patients with non-ST-segment elevation acute coronary syndromes who underwent preintervention coronary computed tomographic angiography and optical coherence tomographic culprit lesion imaging were enrolled. PCAT attenuation was measured around the culprit lesion and in the proximal 40 mm of all coronary arteries., Results: Among 198 patients, plaque rupture was the underlying mechanism in 107 (54.0%) and plaque erosion in 91 (46.0%). Plaque rupture had higher PCAT attenuation than plaque erosion both at the culprit plaque level (-65.8 ± 7.5 HU vs -69.5 ± 11.4 HU; P = 0.010) and at the culprit vessel level (-67.1 ± 7.1 HU vs -69.6 ± 8.2 HU; P = 0.024). The mean PCAT attenuation of all 3 coronary arteries was also significantly higher in patients with plaque rupture than in plaque erosion, indicating a higher level of inflammation (-67.9 ± 5.7 HU vs -69.9 ± 6.8 HU; P = 0.030). In multivariable analysis, plaque rupture was significantly associated with high PCAT attenuation., Conclusions: PCAT attenuation in culprit plaque, culprit vessel, and all 3 coronary arteries was higher in plaque rupture than in plaque erosion. The results suggest that pancoronary inflammation plays a more significant role in plaque rupture than in plaque erosion. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194)., Competing Interests: Funding Support and Author Disclosures Dr Jang’s research was supported by Mr and Mrs Allan and Gill Gray and by Mr and Mrs Michael and Kathryn Park. Dr Dey is supported by National Heart, Lung, and Blood Institute grants (1R01HL148787-01A1 and 1R01HL151266). The funders had no role in the design or conduct of this research. Dr Jang has received educational grant support from Abbott Vascular; and consulting fees from Svelte Medical Systems and Mitobridge. Outside the present study, Dr Dey has received software royalties from Cedars-Sinai Medical Center; and has a patent. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to describe the potential of 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression., Background: As well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis., Methods: Patients with established coronary artery disease underwent baseline 18 F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18 F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery., Results: Among 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18 F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting., Conclusions: Native coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy., Competing Interests: Funding Support and Author Disclosures This research was supported in part by grant R01HL135557 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Newby (CH/09/002, RE/18/5/34216, RG/16/10/32375), Dr Tzolos (FS/CRTF/20/24086), Dr Fletcher (FS/19/15/34155), Dr Baker (RG/20/5/34796), Dr Dweck (FS/14/78/31020), and Dr Williams (FS/ICRF/20/26002) are supported by the British Heart Foundation. Dr Adamson is supported by a Heart Foundation of New Zealand Senior Fellowship (1844). Dr van Beek is supported by the Scottish Imaging Network. Dr Tzolos was supported by a grant from the Dr Miriam and Sheldon G. Adelson Medical Research Foundation. Dr Newby is a recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr Dweck is a recipient of the Sir Jules Thorn Award for Biomedical Research Award (2015). Dr Sellers is supported by fellowships from the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)